Clinical Impact of Drug Use in HIV-Infected Persons: A Pilot Study

HIV 感染者吸毒的临床影响：一项试点研究

• 批准号: 7546829
• 负责人: JEFFREY H. SAMET
• 金额: $ 13.38万
• 依托单位: BOSTON MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7546829
• 关键词: AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Adherence; Adult; Affect; Alcohol consumption; Alcohol or Other Drugs use; Anti-HIV Agents; Anti-Retroviral Agents; Biological; CD4 Lymphocyte Count; Caring; Characteristics; Clinical; Clinical Trials; Cohort Studies; Collaborations; Data; Data Reporting; Disease Progression; Drug Administration Routes; Drug abuse; Drug usage; Drug user; Epidemic; Foundations; Future; Goals; HIV; HIV Infections; HIV diagnosis; Hair; Health; Health Occupations; Health Professional; Health Status; Hepatitis C virus; Illicit Drugs; Immune response; Immunologics; Individual; Infection; Injection of therapeutic agent; International; Lead; Measures; Mediating; Medical; Mental Depression; Numbers; Outcome; Pathway interactions; Patient Self-Report; Patients; Pattern; Persons; Pharmaceutical Preparations; Physiological; Pilot Projects; Play; Policy Maker; Protocols documentation; Public Health; RNA; Range; Rate; Recording of previous events; Recruitment Activity; Research; Research Activity; Research Infrastructure; Research Project Grants; Resistance; Resistance development; Risk; Role; Route; Russia; Sampling; Site; Testing; Toxicology; United States; United States National Institutes of Health; Urine; Viral; Viral Load result; addiction; antiretroviral therapy; base; cohort; demographics; design; drug of abuse; experience; improved; medication compliance; response; size

DESCRIPTION (provided by applicant): Drug abuse plays a prominent role in the HIV epidemic in Russia; nearly 80% of cases are attributed to injection drug use. A history of drug use or continued use after an HIV diagnosis can lead to negative health consequences. Drug use may hinder efforts to engage patients in medical care including use of antiretroviral treatment (ART). A direct physiologic impact of drugs of abuse on HIV disease progression has not been clearly documented despite immunologic findings suggesting a rational basis for such an association. Hence, a variety of factors associated with drug use may place the HIV-infected drug user at increased risk for more rapid HIV disease progression. However, clear evidence of an independent association between drug abuse and HIV disease progression awaits further study. The primary goal of this research initiative is to investigate the relationship between drug abuse and HIV disease progression by utilizing a currently developing cohort of 700 HIV-infected adults in Russia, many with a prior history of injection drug use. This 1-year R21 pilot study, "Drug Use IMPACT" (Investigating and Measuring Progression to AIDS in a Cohort Trial), will lay important groundwork for the design of a future longitudinal research initiative that can more definitively assess the relationship between drug use and HIV disease progression. The Specific Aims are: 1. Use an existing cohort of HIV-infected Russians to assess markers of HIV disease progression (i.e., CD4 cell count, HIV viral load [HIV RNA]) and confounding factors. 2. Estimate the effect size of drug use on markers of HIV disease progression, controlling for ART use, baseline CD4 cell count, HIV RNA (for CD4 outcome), alcohol use, depression, and sociodemographics. 3. Explore potential mechanisms by which drug use worsens HIV disease progression (e.g. reduced access to ART, increased alcohol use, depression, and HCV co-infection). We will recruit 100 subjects from an existing NIH study and collect additional self-report data on medication adherence and drug use. We will collect biological samples to assess CD4 cell count, HIV RNA, and drug use (urine toxicology on all and hair toxicology on a subsample). These data will be combined with data already available on the cohort (e.g. alcohol use, demographics). We hypothesize that illicit drug use is independently associated with more rapid HIV disease progression, as measured by CD4 cell count and HIV viral load. The data generated from this study will allow us to conduct preliminary tests of this hypothesis. Specifically, it will provide important effect size estimates that will be useful for designing a future cohort study that follows subjects longitudinally over several years to fully characterize the relationship between drug abuse and HIV disease progression. The primary analysis will be on any current drug use; however, the effects of specific drug use characteristics (i.e., specific drug, route of administration, exposure duration) will be explored in secondary analyses. Evidence suggests a relationship between drug use and worse HIV disease progression but the study of this relationship in the United States is complicated by several important confounders: unknown individual duration of HIV infection in an epidemic three decades old; substance use that frequently involves multiple drugs; longstanding use of ART with associated viral resistant strains; and common ART use which has a dominant effect on HIV disease progression. Each of these confounders is mitigated in the current Russian setting, making it a promising site to examine both the association between drug use and HIV disease progression, and the potential pathways that may mediate such a relationship. Elucidation of the relationship of drug use to HIV disease progression will facilitate efforts by clinicians, public health professions, and policy makers to improve the medical care, addiction treatment, and ultimately the health status of HIV-infected drug users.

药物滥用在俄罗斯的艾滋病毒流行中起着重要作用;近80%的病例归因于注射毒品。吸毒史或在艾滋病毒诊断后继续吸毒可能导致负面的健康后果。吸毒可能会阻碍患者接受医疗护理，包括使用抗逆转录病毒治疗。药物滥用对HIV疾病进展的直接生理影响尚未明确记录，尽管免疫学研究结果表明这种关联的合理基础。因此，与吸毒有关的各种因素可能会使感染艾滋病毒的吸毒者面临更快的艾滋病毒疾病进展的风险增加。然而，药物滥用与艾滋病毒疾病进展之间存在独立关联的明确证据有待进一步研究。这项研究计划的主要目标是调查药物滥用和艾滋病毒疾病进展之间的关系，利用目前正在发展的队列700名艾滋病毒感染的成年人在俄罗斯，许多人有注射吸毒史。这项为期一年的R21试点研究，“药物使用影响”（队列试验中艾滋病进展的调查和测量），将为设计未来的纵向研究计划奠定重要基础，该计划可以更明确地评估药物使用与艾滋病毒疾病进展之间的关系。具体目标是：1。使用现有的俄罗斯HIV感染者队列来评估HIV疾病进展的标志物（即，CD 4细胞计数、HIV病毒载量[HIV RNA]）和混杂因素。2.估计药物使用对HIV疾病进展标志物的影响大小，控制ART使用，基线CD 4细胞计数，HIV RNA（用于CD 4结果），酒精使用，抑郁症和社会人口统计学。3.探索药物使用加速HIV疾病进展的潜在机制（例如，ART获得减少，酒精使用增加，抑郁症和HCV合并感染）。我们将从现有的NIH研究中招募100名受试者，并收集有关药物依从性和药物使用的其他自我报告数据。我们将收集生物样本，以评估CD 4细胞计数、HIV RNA和药物使用（所有样本的尿液毒理学和子样本的毛发毒理学）。这些数据将与队列中已有的数据（例如酒精使用、人口统计学）相结合。我们假设，非法药物的使用与更快的HIV疾病进展独立相关，如通过CD 4细胞计数和HIV病毒载量测量的。这项研究产生的数据将使我们能够对这一假设进行初步检验。具体而言，它将提供重要的效应量估计值，这将有助于设计未来的队列研究，该研究将纵向跟踪受试者数年，以充分表征药物滥用与HIV疾病进展之间的关系。主要分析将针对任何当前药物使用;然而，特定药物使用特征（即，具体药物、给药途径、暴露持续时间）。证据表明药物使用与更严重的HIV疾病进展之间存在关系，但在美国对这种关系的研究因几个重要的混杂因素而变得复杂：在三十年的流行病中，HIV感染的个体持续时间未知;经常涉及多种药物的物质使用;长期使用ART与相关的病毒耐药株;以及常见的ART使用对HIV疾病进展具有主导作用。在当前的俄罗斯环境中，这些混杂因素中的每一个都得到了缓解，使其成为研究药物使用与艾滋病毒疾病进展之间的关联以及可能介导这种关系的潜在途径的有希望的地点。阐明药物使用与HIV疾病进展的关系将有助于临床医生、公共卫生专业人员和政策制定者努力改善医疗保健、成瘾治疗，并最终改善HIV感染药物使用者的健康状况。